Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma

Abstract

AIM:To investigate the mechanism and significance of NF-κB activation regulated by hepatitis B virus X protein (HBx) in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). METHODS:The expression levels of HBx, p65, IκB-α and ubiquitin were detected by immunohistochemistry in HCC tissue microarrays (TMA) respectively, and IκB-α was detected by Western blot in HCC and corresponding liver tissues. RESULTS:The percentage of informative TMA samples was 98.8% in 186 cases with a total of 367 samples. Compared with corresponding liver tissues (60.0%), the HBx expression was obviously decreased in HBV-associated HCC (47. 9%, u=2.24, P<0.05). On the contrary, the expressions of p65 (20.6% vs 45.3%, u=4.85, P<0.01) and ubiquitin (8.9% vs 59.0%, u=9.68, P<0.01) were notably elevated in HCC. In addition, IκB-α had a tendency to go up. Importantly, positive relativity was observed between HBx and p65 (χ Wang T, Wang Y, Wu MC, Guan XY, Yin ZF. Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma.

Expression of Tyrosine Kinase Etk/Bmx and Its Relationship with AP-1- and NF-κB-Associated Proteins in Hepatocellular Carcinoma

“…Aberrant activation of NF-ĸB p65 was also present in HCC in this study as in a previous report [30]. We further observed a more frequent expression of NF-ĸB p65 in Etk/Bmx-positive HCC cases than in Etk/Bmx-negative cases, but the difference was not statistically significant.…”

HBx-Induced Hepatic Steatosis and Apoptosis Are Regulated by TNFR1- and NF-κB-Dependent Pathways

“…Increasing evidence suggests that HBx-mediated nuclear factor κB (NF-κB) activation has been implicated in hepatic inflammation, regeneration, liver injury, and HCC. 6 In our previous report, the association between HBx-mediated NF-κB activation and TNF receptor 1 (TNFR1) has been suggested, 7 but our report lacked information regarding HBx involvement in the TNFR1 pathway, and how HBx stimulates NF-κB activity through TNFR1 has yet to be determined.…”

“…On the other hand, it has been demonstrated that HBx-activated NF-κB prevented mitochondria membrane depolarization and apoptosis, 17 but increasing evidences suggest that HBx-mediated NF-κB activation has also been implicated in hepatic inflammation, regeneration, liver injury, and HCC. 6 Furthermore, the impacts of HBx on hepatocyte apoptosis are also different, depending on additional orchestrated signals such as TNF-α or ethanol. 20 Our data have also shown that similar to the role of NF-κB activation in HBxinduced steatosis, NF-κB activation is also associated with fulminant hepatitis induced by HBx/ TNF-α and, especially, activated NF-κB is required for the induction of apoptosis through ROS production and loss of mitochondrial membrane potential induced by HBx/TNF-α (Fig.…”

Interferon-alpha restrains growth and invasive potential of hepatocellular carcinoma induced by hepatitis B virus X protein

“…Some studies have shown that HBx can induce tumor proliferation and invasion through down-regulating the function of P53 [23,24] , up-regulating the expression of survivin [25] , activating with several important cell signaling pathways, including PKB/Akt [26] , RAS/RAF/MAPK [27] , wnt/β-catenin [28] and NF-κB [29] . It has also proved that www.wjgnet.com…”